Scientific Session Highlights

Infectious disease expert Gregory A. Poland, MACP, is upset about the bad rep that vaccines have gotten lately. He’s even created a quasi music video correcting popular misconceptions about vaccination.

Dr. Poland screened the video and provided a wide-ranging update on the topic during yesterday morning’s session “Adult Immunizations.” In addition to promoting the use of vaccines, he reminded physicians about some common errors in administration.

The pneumococcus vaccine is a prime area of confusion. The common practice of referring to the shot as the pneumonia vaccine causes misunderstanding about its effects, Dr. Poland said. “It’s important. This vaccine does not protect against pneumonia. It is protective against the invasive complications, such as bacteremia.”

It’s also important to know how many times to give the vaccine to a patient—which is just once in the majority of patients. Administering the vaccine every five years, as some providers mistakenly do, may actually be harmful. There is no evidence support for any boosters, except among a few patient groups (those who are immunocompromised, have organ transplants, or got the vaccine before age 65) who should get a second dose. “This was published once and—bingo—it got into the clinical lore immediately,” Dr. Poland said.

There are new recommendations calling for administration of the vaccine to smokers and asthmatics, he noted. Dr. Poland also recommended that physicians give the vaccine intramuscularly instead of subcutaneously to reduce the chance of adverse reactions.

On the subject of adverse reactions, Dr. Poland reviewed data showing that there are very few reasons for health care workers not to get influenza vaccines and very many reasons why they should.

“It’s not about you. It’s to protect the patients you care for,” he said. “We know that influenza immunization of health care workers significantly decreases morbidity and mortality.”

Research has shown that vaccination of health care workers can have a much greater effect on patient mortality than vaccinating the patients themselves (since the sick and elderly have less response to the vaccine) and can reduce mortality rates in the intensive care unit by as much as 60%.

And if the benefits to patients aren’t convincing enough, do it for yourself, said Dr. Poland. Since ACP and a number of other groups have come out in support of vaccinating all health care workers, flu vaccination has become a standard of care, applicable in malpractice cases. “The lawyers note this now. You put yourselves and your hospital at risk when you don’t follow this standard of care,” he said.

Dr. Poland was also convincing on the merits of the zoster vaccine, which reduces incidence of the disease by half and post-herpetic neuralgia—the very common, very unpleasant complication—by two-thirds.

“It’s not a home run in terms of protection, but significantly helpful in reducing the burden of zoster,” he noted. The vaccine is currently recommended for patients 60 and older who are otherwise healthy, regardless of their history of shingles. If patients have had shingles, the expert consensus is to wait at least 12 months before vaccinating, Dr. Poland said.

Predicting risk is next challenge in tackling breast cancer

Improvements in breast cancer prevention and screening have led to declining mortality rates over the last 30 years, but with that progress comes a new challenge for internists: how to decide who gets what?

"We have many new tools now, but it's hard to figure out who should use them," said Katrina Armstrong, FACP, who led a Thursday morning session on breast cancer prevention and screening. "Over the next 10 years, I expect to see substantial changes in the area of risk prediction."

Currently, there are three major ways to predict risk: identification of major risk factors such as BRCA1 and 2 mutations, family history-based models, and the "old standby" Gail Model, said Dr. Armstrong, associate professor of general internal medicine at the University of Pennsylvania. Family history is the best indicator of risk, she said, but it is time-consuming and often not practical at the point of care. And getting an accurate picture of genetic risk is complicated by the confusing array of tools currently available on the Web and the difficulty of assessing their validity in the absence of federal regulations, she added.

Advances in chemoprevention using the selective estrogen receptor modulators tamoxifen and raloxifene have successfully prevented or delayed some cancers in high-risk women, Dr. Armstrong explained. However, tamoxifen has multiple side effects, including endometrial cancer, deep venous thrombosis and cataracts. Raloxifene has fewer, but still significant, side effects, such as increased risk of stroke.

"We have two imperfect drugs that we know can prevent breast cancer, but there are tradeoffs," said Dr. Armstrong. "The likelihood of benefit increases as a woman's risk of breast cancer increases," she added. Level of risk and patient preferences should factor heavily into a woman's decision to choose chemoprevention.

In the area of screening, magnetic resonance imaging (MRI) has become an important tool in detecting cancers in high-risk women, she said, and the American Cancer Society recommends it for women with an approximately 20% to 25% or greater lifetime risk of breast cancer. However, while MRI screening has greater sensitivity, there is no evidence to date that it leads to decreased mortality.

Dr. Armstrong listed these four major risk factors, any one of which would classify a woman as at high risk for breast cancer: BRCA1 or 2 mutation; prior chest irradiation (such as for Hodgkin's disease); lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS); and certain rare genetic disorders such as Cowden or Li-Fraumeni syndromes.

Cost and access are often major obstacles to implementing appropriate interventions, said Dr. Armstrong. BRCA testing, screening MRI and chemoprevention carry hefty price tags that often must be borne by patients. In addition, availability of interventions varies geographically, with more options available to women in major metropolitan areas than in rural areas.

"We can do all these studies on disparities but it often comes down to price, and the costs are not trivial," she said. "We can't move to using new technologies unless we can determine if the costs can be reduced to improve access."

So many drugs, so many interactions

How do you know if your patient is at risk for a drug interaction? Douglas S. Paauw, FACP, has one easy rule of thumb. “Once somebody is on more than 10 drugs, the likelihood of a drug interaction is yes,” he told precourse attendees on Wednesday.

Even patients taking fewer drugs risk serious harm from some common interactions and side effects, he noted. The session reviewed a few of those issues most likely to come up in an internal medicine practice.

There are quite a few drugs that interfere with the absorption of thyroid-stimulating hormone (TSH), for example. If a patient on thyroid replacement therapy has an increase in TSH, the culprit could be iron or calcium supplements, a binder like sucralfate or cholestyramine, or a proton pump inhibitor (PPI).

“Anything that decreases stomach acid can affect thyroid hormone,” said Dr. Paauw. A number of potential problems with PPI use have come up recently, including decreased absorption of calcium, iron and antifungals and an increased risk of Clostridium difficile.

“We’re seeing more and more of a push to limit our PPI use. We should put them on the lowest dose that gets the job done,” he said.

Aiming for a low dose is also appropriate in statin therapy, Dr. Paauw said, acknowledging that cardiologists might disagree with him.

About 10%-15% of patients suffer muscle pain or weakness on statins, and biopsies have shown that all statin patients, even asymptomatic ones, have muscle cell damage from the drugs. That data gives Dr. Paauw pause about prescribing statins to young patients, too. “My concern is, what is the effect over 40 years if everybody has muscle damage?” he asked.

Statins are also one of the drugs most likely to interact with grapefruit juice. Even medication timing (pills at night, juice in the morning) does not fully correct for the effect, Dr. Paauw warned. Also on the list of grapefruit-affected drugs are cyclosporine, saquinavir, benzodiazepines and calcium channel blockers.

But if you’re looking for the drugs that can have dramatically bad interactions, watch out for warfarin, Dr. Paauw said. Antibiotics, particularly trimethoprim and sulfamethoxazole, double strength, can have a significant effect on International Normalized Ratio. He also warned about the effects of corticosteroids and acetaminophen on warfarin.

The problem arises with sustained, not occasional, use of acetaminophen, Dr. Paauw noted. “Most of us will tell our patients take acetaminophen for an ache or pain. The problem is when they’re taking it regularly.”

Bleeding risk is also something to keep in mind when prescribing selective serotonin reuptake inhibitors (SSRI). Two retrospective studies have shown an increased risk of upper gastrointestinal bleeds in patients who are taking the drugs. The risk is heightened when patients are also taking a non-steroidal anti-inflammatory, and patients who are on both should get some form of gastroprotection, Dr. Paauw said. “We need to stop before putting SSRIs in the drinking water,” he joked.

After an hour of Dr. Paauw’s warnings on drug effects and interactions—which also included issues with thiazolidinediones, loop diuretics and bisphosphonates, attendees would likely think twice before putting any drugs in the water.

Aspirin, other agents considered for colon cancer

While baby aspirin can be effective for prevention of coronary heart disease, the adult dose may prevent polyps' progression to colon cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain a compelling option, said Robert J. Mayer, FACP, a medical oncologist at the Dana-Farber Cancer Institute at Harvard. He highlighted the probable, possible and unlikely options for how dietary and other supplements might affect colon cancer.

Data are most compelling for aspirin, based on evidence from prospective cohort studies such as the Nurses' Health Study, which has examined 120,000 people since 1976.

There appears to be a dose-dependant reduction in cancer mortality among a subgroup of nearly 83,000 women examined in the Nurses' Health Study from 1980-2000. There was a one-third reduction for those taking more than 14 aspirin tablets each week (P<0.001).

"This is cohort observation," Dr. Mayer said, "but the numbers here are so large, and there are so many other data that support this with a dose relationship, that I think most of us have accepted this observation."

Aspirin is thought to have an antiproliferative effect both early and later in the progression of adenomatous polyps to cancer. It is thought to block the initial step of normal mucosal epithelium progressing to hyperproliferative epithelium and again from that stage to small adenomas. NSAIDs are thought to inhibit COX-2, part of the prostaglandin cycle that stimulates the bowel lining. Other supplements show more promise than proof.

Folic acid earned a "perhaps" from Dr. Mayer during the presentation, because it's suspected to stabilize DNA and prevent demethylation. And it's added as a supplement to bread products, so it's hard to become folate depleted in America.

Estrogen replacement therapy is out of fashion for menopause, he said, but in the colon, it decreases insulin-like growth factor, a stimulant for proliferation of the mucosa. Obese people with type 2 diabetes have an increased amount of insulin-like growth factor and the obese are at higher risk of colon cancer.

"Even though I haven't seen those two dots connected yet, estrogen may be inhibiting that step," Dr. Mayer said.

Americans tend to have low serum vitamin D levels, with only 20% of it coming from diet. But supplements can increase serum concentration, and the highest vitamin D concentration confers a significant reduction in mortality from colon cancer. In the Nurses' Health Study, levels of vitamin D of 25 ng/mL or more conferred a 47% reduction in mortality. Prospective study is needed, Dr. Mayer added.

But two crucial therapies, fiber and vitamin E, don't work. Fiber was first speculated upon by a British surgeon stationed in Africa, but the research did not hold up when considering the disparities of meat consumed by the African and English populations, Dr. Mayer said.

Antioxidants have no effect, Dr. Mayer said, adding, "Many of our patients would like to believe that ascorbic acid, beta-carotene and vitamin E are preventative. There now are prospective data that show that there does not appear to be any medical (benefit) whatsoever."

The new ACP COPD Portal debuted at Internal medicine 2009, providing concise answers to specific clinical and practice-management questions for internists, other health care professionals, and patients and their families.

It was a small feeding of the mind to put you off feeding. Yesterday's lecture by Louis Arronne, FACP, reviewed all the negative consequences of obesity and offered a few additional tidbits. Find out more on ACP Internist's blog, updated each day during Internal Medicine 2009.

For Attendees

Recent guidelines on diagnosis, surveillance and therapy for Barrett's esophagus will highlight today's update in gastroenterology at 11:15 a.m. in Marriott Salon H (course handout: handouts are available to attendees of Internal Medicine 2009).

The incidence of Barrett's esophagus has increased in recent years but it remains a challenging diagnosis because patients who have it often present without any reflux symptoms, said Norton J. Greenberger, MACP, clinical professor of medicine at Harvard Medical School, co-presenter of the update with Prateek Sharma, FACP, professor of medicine at Kansas University School of Medicine.

The annual risk of esophageal adenocarcinoma in Caucasian men is 3.6 per 100,000, with men older than age 50 most often affected. Evidence suggests that surveillance is effective, said Dr. Greenberger, and that frequency should depend on the degree of dysplasia. If no dysplasia is evident, for example, endoscopy once every three years is sufficient, whereas high-grade dysplasia may require endoscopic resection and continued surveillance every three months. Drs. Greenberger and Sharma also will discuss current thinking about using proton-pump inhibitors (PPIs) to control reflux symptoms.

Other highlights of the update will include:

Eosinophilic esophagitis. The disease, which affects all ages, is often overlooked because it is relatively rare and often difficult to diagnose, said Dr. Greenberger. Dysphagia is the most common symptom in adults, followed by reflex/heartburn, and endoscopy with biopsies is the only way to reach a definitive diagnosis. The presenters will review slides of eosinophils from a national pathology database reviewed by pathologists and discuss current treatment strategies, which include dietary therapies and topical corticosteroids.

Gastroprotective strategies in chronic users of nonsteroidal anti-inflammatory drugs (NSAIDs). A recently published population-based match control-case analysis based on the Manitoba Population Health Research Data Repository compared the relative efficacy of different gastroprotective strategies in long-term users of NSAIDs. Researchers concluded that a combination of a COX-2 inhibitor and PPI results in the greatest risk reduction for NSAID-related upper GI complications. The risk of a major GI event doubles if a patient on an NSAID is H. pylori positive. Dr. Sharma also will discuss the role of PPI co-therapy in reducing the risk of GI bleeding and other major complications.

Traveler's diarrhea. Discussion will focus on what travelers should do to ensure that they are not being exposed to potentially contaminated foods. Certain foods found in tropical locations—such as fruits and vegetables, moist foods served at room temperature, and tap water—are more likely than others to cause traveler's diarrhea. Caution is key since there are no surefire treatments. Available drugs used for prevention, with different levels of effectiveness, include bismuth subsalicylate, lactobacillus, fluoroquinolones and rifaximin. Dr. Greenberger will describe an algorithm to identify travelers who should take chemoprophylaxis before traveling to high-risk regions.

Nuts, corn and popcorn and the incidence of diverticular disease. A recent study should lay to rest the old dictum that people with diverticular disease can't eat nuts or popcorn, Dr. Greenberger said. The 18-year study, which followed a cohort of 47,228 men age 40-75 years who did not have diverticulosis or complications at baseline, concluded that the recommendation to avoid these foods to prevent colonic diverticular disease should be reconsidered.

Inflammatory bowel disease. Presenters will review the current status of drug therapy for ulcerative colitis and Crohn's disease, including a study that compared the effectiveness of combined immunosuppression with conventional management for Crohn's disease.

Laproscopic antireflux surgery. Presenters will review a study that assessed long-term outcomes for more than 400 patients who underwent laproscopic antireflux surgery. The study indicated that while surgery resolved or improved symptoms such as heartburn, regurgitation, dysphagia and hoarseness in many patients, more than 40% of the patients still were taking reflux medications and 23% were taking PPIs after follow-up. Patients most likely to benefit from the surgery were younger men with predominantly heartburn symptoms.

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